کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5861839 1133766 2014 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Numerical simulations of in vitro nanoparticle toxicity - The case of poly(amido amine) dendrimers
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Numerical simulations of in vitro nanoparticle toxicity - The case of poly(amido amine) dendrimers
چکیده انگلیسی


- The time evolution of oxidative stress and immune response in vitro.
- The dose and generation dependence of oxidative stress.
- The dose dependent viability for different dendrimer nanoparticles.
- The differing responses of different cytotoxic assays and cell lines.

A phenomenological rate equation model is constructed to numerically simulate nanoparticle uptake and subsequent cellular response. Polyamidoamine dendrimers (generations 4-6) are modelled and the temporal evolution of the intracellular cascade of; increased levels of reactive oxygen species, intracellular antioxidant species, caspase activation, mitochondrial membrane potential decay, tumour necrosis factor and interleukin generation is simulated, based on experimental observations.The dose and generation dependence of several of these response factors are seen to well represent experimental observations at a range of time points. The model indicates that variations between responses of different cell-lines, including murine macrophages, human keratinocytes and colon cells, can be simulated and understood in terms of different intracellular antioxidant levels, and, within a given cell-line, varying responses of different cytotoxicity assays can be understood in terms of their sensitivities to different intracellular cascade events.The model serves as a tool to interpolate and visualise the range of dose and temporal dependences and elucidate the mechanisms underlying the in vitro cytotoxic response to nanoparticle exposure and describes the interaction in terms of independent nanoparticle properties and cellular parameters, based on reaction rates. Such an approach could be a valid alternative to that of effective concentrations for classification of nanotoxicity and may lay the foundation for future quantitative structure activity relationships and predictive nanotoxicity models.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology in Vitro - Volume 28, Issue 8, December 2014, Pages 1449-1460
نویسندگان
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